GLP-1 and the entero-insular axis (the connection between the intestine and the beta-cell)

GLP-1 is a hormone produced by the intestine. Its release is stimulated by food intake. A certain amount of the secernated hormone which reaches the system circulation and target structures in a biologically active form prior to its degradation influences above all insulin secretion – the exocytosis of the granules in the beta cells in the pancreas as much as the biosynthesis of insulin affecting trophically the pancreatic beta cells, influencing the motility of the gastrointestinal tract, decreasing the concentrations of plasmatic glucose and reducing glycemia deviations.

 It brings about the feeling of satiety thus being able to contribute to weight reduction. It has, therefore, an antidiabetic effect too.

GLP-1 inhibits intestine motility thus slowing down the passage through the intestine. It also inhibits gastric emptying in the stomach and the secretion of HCl. It inhibits glucagon secretion. It improves insulin sensitivity, and indicates the feeling of satinity in the central nervous system (CNS) thus resulting in the decrease of body weight by decreasing the food intake. It acts as the incretine hormone in the pancreas stimulating induced food by insulin secretion. GLP-1 stimulates exocytosis of the insulin granules from the pancreatic beta cells.

It also stimulates gene transcription and other biosynthetic processes during insulin synthesis. It leads to beta cells multiplication in the pancreas. It is also possible that apoptosis (the disposal) of beta cells is reduced.

GLP-1 is very quickly degraded in an organism especially by the DPP IV enzyme, its halftime in an organism is approx. 1 – 2 minutes.

In Type 2 diabetics there is described a certain defect in the physiology of incretines: either decreased secretion or increased degradation of incretine hormones, or even both.

The possibilities of GLP-1 employment in the therapy of Type 2 Diabetes Mellitus

This hormone, due to its positive effect on glycemia values, has been investigated as to its possible employment in the diabetes mellitus treatment. Its short lifetime is regarded as a disadvantage which would enable its use only when administered by continuous infusion. This would be, however, not practical and quite impossible.

Scientific teams have succeeded in eliminating this disadvantage by the development of two types of substances:

1. A.    GLP-1 analogues

GLP-1 analogues are substances which have a very similar structure to the hormone itself. They differ, however,in the part of its molecule responsible for its lifetime. These preparations stay in the body for 12 hours now.

They are administered twice a day, their slight disadvantage is that they are applied in the form of a subcutaneous injection,  which is the same as in the case of insulin. Their positive property is body weight decrease during the period of application as proved by several scientific studies.

1. B.    DPP-IV enzyme blockers

DDP-IV enzyme blockers are substances which restrict the effect of the degradation enzyme. Thus the increase in the GLP-1 concentration is achieved and, consequently, its effect is elevated. These preparations are administered orally.